June 25, 2022

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HIV treatment revolution: 365 days changed to 6 days!

HIV treatment revolution: 365 days changed to 6 days!

 

HIV treatment revolution, 365 days changed to 6 days! GSK/Johnson & Johnson complete long-acting therapy.   CAB/RPV: 96 weeks of treatment showed long-term efficacy and safety!

HIV treatment revolution: 365 days changed to 6 days!

ViiV Healthcare is an HIV/AIDS drug research and development company controlled by GlaxoSmithKline (GSK), Pfizer and Shionogi. Recently, the company announced the first complete long-acting program cabotegravir/rilpivirine (CAB/RPV, Cabotevir/Rilpivirine, sustained-release injection suspension) at the 2021 Retroviral and Opportunistic Infection Conference (CRIO).

Positive long-term data from the global phase IIIb ATLAS-2M study on treating HIV. The 96th week data strengthened the 48th week primary endpoint (proportion of patients with plasma HIV-1 RNA ≥50 copies/ml, snapshot, ITT-E) and secondary endpoint (plasma HIV-1 RNA ≥50 or <50 copies/ml Proportion of patients, snapshot, ITT-E).

Current data show that in adult HIV-1 patients who have achieved virological suppression, CAB/RPV once a month and once every 2 months are effective for long-term treatment.

Currently, the CAB/RPV once every 2 months dosing regimen has been approved in the European Union, but has not yet been approved in the United States or Canada. The CAB/RPV program is composed of ViiV’s cabotegravir (CAB, Cabotvir) and Johnson & Johnson’s rilpivirine (RPV, Rilpivirine).

Among them, rilpivirine is a long-acting non-nucleoside reverse transcriptase inhibitor, and cabotegravir is a long-acting HIV-1 integrase chain transfer inhibitor. This complete long-acting solution was developed by ViiV in cooperation with Johnson & Johnson’s Janssen Pharmaceuticals.

In the United States and Canada, the CAB/RPV long-acting regimen has been approved for monthly treatment under the brand name Cabenuva. This is the first and only complete long-acting regimen for the treatment of HIV-1 infection in adults. CAB/RPV indications are: for the treatment of HIV-1 adult infected persons who have received a stable ARV program and have achieved virological suppression (HIV RNA <50 copies/ml), replacing the previous ARV program.

ViiV has submitted a supplementary new drug application to the US FDA to expand the use of Cabenuva as an HIV treatment and include it in a two-month treatment regimen. In Australia, Cabenuva’s monthly and bi-monthly programs have been approved. In addition, the CAB/RPV long-acting program has also been approved in Europe, sold under the brand names Vocabria (cabotegravir) and Rekambys (rilpivirine), and can be treated once a month and once every 2 months.

It is particularly worth mentioning that CAB/RPV is the world’s first complete and long-acting HIV treatment plan, which is administered by intramuscular injection (IM) once a month or every 2 months. The approval of the drug for the market marks a major milestone and will bring a revolution in HIV treatment, changing from oral administration 365 days a year to once a month (12 days a year) or once every 2 months (full 6 days a year).

ATLAS-2M (NCT03299049) is part of CAB/RPV’s extensive innovative clinical project. This is a randomized, open-label, positive-controlled, multi-center, parallel group, non-inferiority phase III study. A total of 1045 HIV cases were enrolled. -1 Adult infected persons, these patients receive first-line or second-line regimen to achieve virological suppression for ≥6 months, and no previous failures. The study evaluated the non-inferiority antiviral activity and safety of CAB/RPV once every 8 weeks (once every 2 months) versus once every 4 weeks (once every 1 month) for 48 weeks. The primary end point was: at the 48th week of treatment, the FDA snapshot algorithm (intention-to-treat exposure [ITT-E] population) was used to determine the proportion of patients with HIV-RNA ≥50c/mL to determine non-inferiority.

The study reached the primary endpoint at the 48th week, confirming that the CAB/RPV once every 8 weeks (once in 2 months) has the same effect as the once every 4 weeks (once in 1 month): treatment of HIV-RNA in the 48th week The proportion of patients with ≥50c/mL is comparable (1.7%[9/522] in the 2-month group, 1.0%[5/523] in the 1-month group, adjusted difference=0.8%[95%CI:- 0.6, 2.2]). The results at the 96th week strengthened the primary endpoint: CAB/RPV once every 8 weeks (once in 2 months) has the same effect as the once every 4 weeks (once in 1 month), and HIV-RNA ≥50c at the 96th week of treatment The proportion of patients per mL is comparable (2.1% [11/522] in the 2-month group, 1.1% in the 1-month group [6/523], adjusted difference = 1.0% [95%CI: -0.6, 2.5]). The 96-week key secondary endpoint showed that the virological inhibition rate (HIV-1 RNA <50c/mL) between the two groups was similar (91.0%[475/522] in the 2-month group and 90.2% in the 1-month group[ 472/523], adjusted difference = 0.8% [95%CI: -2.8, 4.3]).

In this study, confirmed virological failure (CVF) was defined as 2 consecutive viral loads> 200c/mL: data at the 96th week showed that there was 1.7 (9/522) in the 2-month group and 0.4 in the 1-month group %(2/523) CVF appears. The overall incidence of CVF is relatively low (1%, 11/1045). Only one patient in the 2-month group met the CVF criteria in the second year of treatment. This patient developed a rilpivirin resistance-related mutation (RAM) Y181C without Integrase Inhibitor (INSTI) RAM.

The safety profiles between the two treatment groups are comparable, and since the 48th week of analysis, no new safety signals have been found. Injection site reaction (ISR) is the most common adverse event (AE: 16% [74/473] in the administration group every 2 months, 12% in the monthly administration group [54/468]), from week 48 to week One case at 96 weeks resulted in discontinuation of the drug. Most ISR (99%) is mild or moderate and disappears spontaneously, with a median duration of 3 days. During the entire 96 weeks, 1% (7/522) of the patients in the once-a-month dosing group discontinued the drug due to ISR, compared with 2% (11/523) in the once-monthly dosing group.

Hans Jaeger, MD, investigator of the ATLAS-2M study and former medical director of the Munich HIV Research and Clinical Care Center MVZ Karlsplatz, said: “The 96-week data of the ATLAS-2M study strengthens the therapeutic potential of this long-acting regimen. It provides There is a choice that can change the treatment experience of some HIV-infected people and no longer need to take pills every day. This plan can reduce the number of days that HIV-infected people receive treatment from 365 days to 12 or 6 days each year, which represents HIV A paradigm shift in treatment.”

 

(source:internet, reference only)


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